Molecular tools to understand blood-brain barrier function in health, aging, and disease
Abstract/Contents
- Abstract
- Aging is the single greatest risk factor for neurodegenerative disease. Yet amidst an aging global population, there still do not exist effective therapies for such diseases. Recent clinical trials of therapies targeting disease-associated pathology, such as beta-amyloid accumulation in Alzheimer's disease, have found little benefit. Thus, new approaches capable of modifying the underlying process of brain aging are likely needed. Intriguingly, exposure to young blood plasma has been consistently found sufficient to rejuvenate the aging brain. Yet, since the first tracer experiments in 1900, the brain has been believed largely isolated from circulatory proteins via a structure termed the blood-brain barrier (BBB). Here I describe my initial efforts to address this paradox, and in the process, reveal major aspects of BBB function in health and with age. I developed new enzymes for labeling and tracking secreted proteins, and separately, applied single cell transcriptomics to discover the BBB's surprising responsiveness to circulatory proteins. Combining these approaches, I tagged and tracked the blood plasma proteome as a discovery tool to reveal widespread endogenous transport of proteins into the healthy brain and the pharmacologically modifiable mechanisms by which this process becomes impaired with age. These findings suggest the BBB may promote optimal brain function not by its impermeability but by its continuous and organized uptake of plasma proteins, with implications for the pathogenesis of neurodegeneration and the delivery of drugs to treat it.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Yang, Andrew Chris |
|---|---|
| Degree supervisor | Wyss-Coray, Anton |
| Thesis advisor | Wyss-Coray, Anton |
| Thesis advisor | Bertozzi, Carolyn R, 1966- |
| Thesis advisor | Cochran, Jennifer R |
| Degree committee member | Bertozzi, Carolyn R, 1966- |
| Degree committee member | Cochran, Jennifer R |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Andrew Chris Yang. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Andrew Chris Yang
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...